title: Benznidazole microcrystal preparation by solvent change precipitation and in vivo evaluation in the treatment of Chagas disease.
abstract: Benznidazole (BNZ) is traditionally used to treat Chagas disease. Despite its common use, BNZ has a poor water solubility and a variable bioavailability. The purpose of this study was to prepare BNZ microcrystals by solvent change precipitation and to study the effects of BNZ micronisation on therapeutic efficiency using a murine model of Chagas disease. The solvent change precipitation procedure was optimised in order to obtain stable and homogeneous particles with a small particle size, high yield and fast dissolution rate. The thermal and crystallographic analysis showed no polymorphic change in the microcrystals, and microscopy confirmed a significant reduction in particle size. A marked improvement in the drug dissolution rate was observed for micronised BNZ particles and BNZ tablets in comparison with untreated BNZ and commercial Rochagan. In vivo studies showed a significant increase in the therapeutic efficacy of the BNZ microparticles, corroborating the dissolution results.
authors.affiliation: Escola de Farmácia, Universidade Federal de Ouro Preto, Ouro Preto-MG, Brazil.
authors.forename: Flávia Pires
authors.initials: FP
authors.lastname: Maximiano
authors.forename: Lívia Maria
authors.initials: LM
authors.lastname: de Paula
authors.forename: Vivian Paulino
authors.initials: VP
authors.lastname: Figueiredo
authors.forename: Isabel Mayer
authors.initials: IM
authors.lastname: de Andrade
authors.forename: André
authors.initials: A
authors.lastname: Talvani
authors.forename: Lívia C
authors.initials: LC
authors.lastname: Sá-Barreto
authors.forename: Maria Terezinha
authors.initials: MT
authors.lastname: Bahia
authors.forename: Marcílio S S
authors.initials: MS
authors.lastname: Cunha-Filho
mesh_terms: D000818:Animals; D014355:Chagas Disease / Q000188:drug therapy*; D011232:Chemical Precipitation; D004195:Disease Models, Animal; D004339:Drug Compounding / Q000379:methods*; D016503:Drug Delivery Systems; D005079:Excipients; D005260:Female; D006245:Hardness Tests; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D051379:Mice; D009593:Nitroimidazoles / Q000032:analysis / Q000737:chemistry* / Q000627:therapeutic use; D011108:Polymers / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013607:Tablets; D014344:Trypanocidal Agents / Q000032:analysis / Q000737:chemistry* / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects
chemical_list: D005079:Excipients; D009593:Nitroimidazoles; D011108:Polymers; D012997:Solvents; D013607:Tablets; D014344:Trypanocidal Agents; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C009999:benzonidazole